Vitamins

DPT Lectures
Overview:
• Chemically unrelated organic compounds that cannot be synthesized in
adequate quantities by humans and must be supplied by the diet.
• Classified as either water soluble or fat soluble.
• Many water-soluble vitamins are precursors of coenzymes for the
enzymes of metabolism. NAD+ contains niacin and FAD contains riboflavin.
• Fat-soluble vitamins are released, absorbed, and transported with the fat
of the diet. Are not readily excreted in the urine, and significant quantities
are stored in the liver and adipose tissue.
• Excess consumption of Fat soluble vitamins can lead to accumulation of
toxic quantities of these compounds.
Classification:
Holoenzyme - Active enzyme
with its nonprotein
component.
Apoenzyme – Inactive enzyme
without its nonprotein moiety.
Cofactor - Nonprotein moiety
is a metal ion like Zn2+
Coenzyme – Nonprotein
moiety is a small organic
molecule
Water Soluble Vitamins
Folic Acid/Vitamin B9:
• Also known as Vitamin B9
• Folic acid (or folate) plays a key role in one-carbon metabolism and is
essential for the biosynthesis of several compounds.
• Most common vitamin deficiency in the United States.
• Particularly among pregnant women and alcoholics.
• Leafy, dark green vegetables are a good source of folic acid.
Function of Folic Acid – One Carbon
Metabolism
• Tetrahydrofolate (THF) is the reduced,
coenzyme form of folate.
• Receives one-carbon fragments from donors
such as:
• Serine
• Glycine
• Histidine
• Transfers them to intermediates in the synthesis
of:
• Amino acids such as Methionine and Serine
• Purines
• Thymidine monophosphate (TMP)
 Nutritional Anemias:
• Anemia → blood has a lower than normal concentration of
hemoglobin → reduced ability to transport oxygen.
• Nutritional anemias are caused by inadequate intake of one or
more essential nutrients
• Can be classified according to the size of the RBC or Mean
Corpuscular Volume
• Microcytic anemia, caused by lack of iron, is the most common
form of nutritional anemia.
• Macrocytic anemia, results from a deficiency in folic acid or
vitamin B12.
• Macrocytic anemias are commonly called megaloblastic
because of accumulation of large, immature red cell precursors,
known as megaloblasts, in the bone marrow and the blood.
Folate and Anemia
• Inadequate serum levels of folate can be caused by:
• Increased demand (for example, pregnancy and lactation)
• Poor absorption caused by pathology of the small intestine
• Alcoholism
• Treatment with drugs that are dihydrofolate reductase inhibitors, for example,
methotrexate
• Folate-free diet can cause a deficiency within a few weeks.
• Primary result of folic acid deficiency is megaloblastic anemia, caused
by diminished synthesis of purines and TMP → inability of cells
(including red cell precursors) to make DNA.
Folate and Neural Tube Defects
(NTDs)
• Spina bifida and anencephaly are the most common neural tube defects.
• Folic acid supplementation before conception and during the first
trimester has been shown to significantly reduce the defects.
• All women of childbearing age are advised to consume 0.4 mg/day of folic
acid to reduce the risk of having a pregnancy affected by neural tube
defects.
• Critical folate-dependent development occurs in the first weeks of fetal life
• However, there is an association of high-dose supplementation with folic
acid (>0.8 mg/day) and an increased risk of cancer.
• Supplementation is not recommended for most middle-aged or older
adults.
Vitamin B12
• Vitamin B12 is required for two essential
enzymatic reactions:
• Remethylation of homocysteine to methionine
• Isomerization of methylmalonyl coenzyme A (CoA)
• Methylmalonyl CoA is produced during the
degradation of fatty acids with odd numbers of
carbon atoms and some amino acids:
• Isoleucine ∙Threonine
• Methionine ∙Valine
• Deficiency of vitamin B12 can be measured by
the level of methylmalonic acid in blood,
which is elevated.
Structure of cobalamin and its
coenzyme forms
• Cobalamin contains a corrin ring system.
• Differs from the porphyrins - two of the pyrrole rings are linked directly
rather than through a methene bridge.
• Cobalt is held in the center of the corrin ring by 4 coordination bonds from
the nitrogens of the pyrrole groups.
• The remaining coordination bonds of the cobalt are with the nitrogen of
5,6-dimethylbenzimidazole and with cyanide in commercial preparations of
the vitamin in the form of cyanocobalamin
• The coenzyme forms of cobalamin are:
• 5'-deoxy adenosyl–cobalamin
• Methylcobalamin,
Distribution of cobalamin
• Vitamin B12 is synthesized only by microorganisms.
• It is not present in plants.
• Animals obtain the vitamin preformed from their natural bacterial
flora or by eating foods derived from other animals.
• Cobalamin is present in appreciable amounts in liver, whole milk,
eggs, oysters, fresh shrimp, pork, and chicken.
 Folate trap hypothesis:
• Rapidly dividing tissues need both the N5 ,N10- methylene
and N10-formyl forms of tetrahydrofolate for the synthesis of
nucleotides.
• Methylated form cannot be converted directly to other forms
of tetrahydrofolate.
• In vitamin B12 deficiency, the utilization of the N5 -methyl
form of tetrahydrofolate in the B12-dependent methylation
of homo - cysteine to methionine is impaired.
• Folate is trapped in the N5 -methyl form, which accumulates.
• Levels of the other forms decrease.
• Cobalamin deficiency is hypothesized to lead to a deficiency
of the tetrahydrofolate forms needed in purine and TMP
synthesis, resulting in the symptoms of megaloblastic
anemia.
Absorption of Vitamin B12
• Gastric Parietal Cells produce intrinsic factor.
• Vitamin B12 obtained from the diet binds to
intrinsic factor in the intestine.
• Cobalamin–intrinsic factor complex travels
through the gut.
• Eventually binds to specific receptors on the
surface of mucosal cells of the ileum.
• Bound cobalamin is transported into the
mucosal cell and, subsequently, into the general
circulation
• Carried by B12-binding proteins in general
circulation.
Storage
• Significant amounts (4–5 mg) of vitamin B12 are
stored in the body.
• It may take several years for the clinical symptoms
of B12 deficiency to develop.
• Mostly seen in individuals who have had a partial
or total gastrectomy.
• Deficiency of intrinsic factor.
Pernicious Anemia
• Deficiency of B12 is rarely a result of an absence of the vitamin in the diet.
• Malabsorption is more common.
• In the elderly is most often due to reduced secretion of gastric acid and less efficient
absorption of vitamin B12 from foods.
• Pernicious Anemia:
• Autoimmune destruction of the gastric parietal cells
• Lack of intrinsic factor prevents the absorption of vitamin B12.
• Patients usually anemic, but later in the the disease they show neuropsychiatric
symptoms.
• Central nervous system (CNS) symptoms may occur in the absence of anemia and are
irreversible .
• Treated by giving high-dose B12 orally, or IM injection of cyanocobalamin.
• Therapy must be continued throughout the lives of patients with pernicious anemia.
Two Scenarios
• An elderly man complaining of tingling in his feet and memory issues,
visits the clinic. His blood work reveals macrocytic anemia and
significantly elevated levels of methylmalonic acid. He has a history of
partial gastrectomy 3 years back. What is the likely diagnosis?

VS
• A 30-year-old pregnant woman presents with severe fatigue and
pallor. Lab tests reveal macrocytic anemia. She admits to a diet
lacking in green leafy vegetables. What is the likely diagnosis?
Two Scenarios
• An elderly man complaining of tingling in his feet and memory issues,
visits the clinic. His blood work reveals macrocytic anemia and
significantly elevated levels of methylmalonic acid. He has a history of
partial gastrectomy 3 years back. What is the likely diagnosis?

VS
• A 30-year-old pregnant woman presents with severe fatigue and
pallor. Lab tests reveal macrocytic anemia. She admits to a diet
lacking in green leafy vegetables. Her symptoms are expected to
resolve with treatment and dietary changes.
Thankyou!
Ascorbic Acid (Vitamin C)
• The active form of vitamin C is ascorbic acid.
• Main function of ascorbate is as a reducing agent in
several different reactions.
• Well-documented role as a coenzyme in
hydroxylation reactions, for example, hydroxylation
of prolyl and lysyl residues of collagen
• Required for the maintenance of normal connective
tissue and wound healing.
• Also facilitates the absorption of dietary iron from
the intestine.
• Anti-oxidant.
Deficiency of Vitamin C

• A deficiency of ascorbic acid results in scurvy characterized by:

• Sore and spongy gums
• Loose teeth
• Fragile blood vessels
• Swollen joints
• Anemia
• Many of the deficiency symptoms can be explained by a deficiency in
the hydroxylation of collagen, resulting in defective connective tissue.
Prevention of chronic disease:
• Vitamin C is one of a group of nutrients that includes vitamin E and β-
carotene which are known as anti-oxidants.
• Consumption of diets rich in these compounds is associated with a
decreased incidence chronic diseases such as coronary heart disease
and certain cancers.
Pyridoxine (Vitamin B6)
• Vitamin B6 is a collective term for pyridoxine,
pyridoxal, and pyridoxamine, all derivatives of pyridine.
• Differ only in the nature of the functional group
attached to the ring
• Pyridoxine occurs primarily in plants, pyridoxal and
pyridoxamine are found in foods obtained from
animals.
• All three compounds can serve as precursors of the
biologically active coenzyme, pyridoxal phosphate.
• Pyridoxal phosphate functions as a coenzyme for a
large number of enzymes, particularly those that
catalyze reactions involving amino acids.
Clinical Indications:
• Isoniazid (isonicotinic acid hydrazide), is a drug frequently used to
treat tuberculosis, can induce a vitamin B6 deficiency by forming an
inactive derivative with pyridoxal phosphate.
• Dietary supplementation with B6 is, thus, an adjunct to isoniazid
treatment.
• Dietary deficiencies in pyridoxine are rare but have been observed in:
• Newborn infants fed formulas low in B6.
• Women taking oral contraceptives
• Alcoholics
Toxicity
• Only water-soluble vitamin with significant toxicity.
• Neurologic symptoms (sensory neuropathy) occur at intakes above
200 mg/day, an amount more than 100 times the RDA.
• Substantial improvement, but not complete recovery, occurs when
the vitamin is discontinued.
Thiamine (Vitamin B1)
• Thiamine pyrophosphate (TPP) is the biologically active
form of the vitamin.
• Formed by the transfer of a pyrophosphate group from
adenosine triphosphate (ATP) to thiamine
• Thiamine pyrophosphate serves as a coenzyme in:
• The formation or degradation of α-ketols by transketolase
• The oxidative decarboxylation of α-keto acids.
Thiamine (Vitamin B1)
• Thiamine pyrophosphate (TPP) is the biologically
active form of the vitamin.
• Formed by the transfer of a pyrophosphate group
from adenosine triphosphate (ATP) to thiamine
• Thiamine pyrophosphate serves as a coenzyme in:
• The formation or degradation of α-ketols by
transketolase
• The oxidative decarboxylation of α-keto acids.
• Oxidative decarboxylation of pyruvate and α-ketoglutarate, which
plays a key role in energy metabolism of most cells, is particularly
important in tissues of the nervous system.
• In thiamine deficiency, the activity of these two dehydrogenase-
catalyzed reactions is decreased, resulting in a decreased production
of ATP and, thus, impaired cellular function.
• Thiamine deficiency is diagnosed by an increase in erythrocyte
transketolase activity observed on addition of thiamine
pyrophosphate.
Beri-Beri
• Severe thiamine-deficiency syndrome found in areas where polished
rice is the major component of the diet.
• Signs of infantile beriberi include tachycardia, vomiting, convulsions,
and, if not treated, death.
• Can have a rapid onset in nursing infants whose mothers are deficient
in thiamine.
• Adult beriberi is characterized by dry skin, irritability, disordered
thinking, and progressive paralysis.
Wernicke-Korsakoff syndrome:
• Thiamine deficiency, seen primarily in association with chronic
alcoholism, is due to dietary insufficiency or impaired intestinal
absorption of the vitamin.
• Some alcoholics develop Wernicke-Korsakoff syndrome.
• A thiamine deficiency state characterized by apathy, loss of memory,
ataxia, and a rhythmic to-and-fro motion of the eyeballs (nystagmus).
• Neurologic consequences of Wernicke's syndrome are treatable with
thiamine supplementation.
Niacin
• Niacin, or nicotinic acid, is a substituted pyridine derivative.
• Biologically active coenzyme forms are:
• Nicotinamide adenine dinucleotide (NAD+)
• and its phosphorylated derivative, nicotinamide adenine dinucleotide
phosphate (NADP+).
• NAD+ and NADP+ serve as coenzymes in oxidation-reduction
reactions in which the coenzyme undergoes reduction of the pyridine
ring by accepting a hydride ion.
• The reduced forms of NAD+ and NADP+ are NADH and NADPH,
respectively.
• Niacin is found in unrefined and enriched grains and cereals, as well
as in milk and lean meats, particularly liver.
• Corn is low in both niacin and tryptophan. Corn-based diets can cause
pellagra.
Pallegra
• A deficiency of niacin causes pellagra, a disease involving the skin,
gastrointestinal tract, and CNS.
• The symptoms of pellagra progress through the three Ds: dermatitis,
diarrhea, dementia—and, if untreated, death.
 Niacin for the treatment of
hyperlipidemias:
• Niacin (at doses of 1.5 g/day or 100 times the Recommended Dietary Allowance
or RDA) strongly inhibits lipolysis in adipose tissue.
• The liver normally uses these circulating fatty acids as a major precursor for
triacylglycerol synthesis.
• Thus, niacin causes a decrease in liver triacylglycerol synthesis, which is required
for very-low-density lipoprotein production.
• Low-density lipoprotein (LDL, the cholesterol-rich lipoprotein) is derived from
VLDL in the plasma.
• Thus, both plasma triacylglycerol (in VLDL) and cholesterol (in VLDL and LDL) are
lowered.
• Therefore, niacin is particularly useful in the treatment of Type IIb
hyperlipoproteinemia, in which both VLDL and LDL are elevated.
Riboflavin / Vitamin B2
• The two biologically active forms are:
• Flavin mononucleotide (FMN)
• Flavin adenine dinucleotide (FAD)
Riboflavin / Vitamin B2
• FMN and FAD are bound tightly—sometimes covalently—to
flavoenzymes that catalyze the oxidation or reduction of a substrate.
• Riboflavin deficiency is not associated with a major human disease,
• Frequently accompanies other vitamin deficiencies.
• Deficiency symptoms include:
• Dermatitis
• Cheilosis (fissuring at the corners of the mouth)
• Glossitis (the tongue appearing smooth and purplish).
 Pantothenic Acid/Vitamin B5
• Pantothenic acid is a component of coenzyme A (CoA),
which functions in the transfer of acyl groups.
• CoA contains a thiol group that carries acyl compounds
as activated thiol esters.
• Examples of such structures are succinyl CoA, fatty acyl
CoA, and acetyl CoA.
• Pantothenic acid is also a component of the acyl carrier
protein (ACP) domain of fatty acid synthase.
• Eggs, liver, and yeast are the most important sources of
pantothenic acid, although the vitamin is widely
distributed.
• Pantothenic acid deficiency is not well characterized in
humans, and no RDA has been established.
Biotin/Vitamin B7
• Biotin is a coenzyme in carboxylation reactions, in
which it serves as a carrier of activated carbon
dioxide
• Biotin is covalently bound to the ε-amino groups of
lysine residues in biotin-dependent enzymes
• Biotin deficiency does not occur naturally because
the vitamin is widely distributed in food.
• A large percentage of the biotin requirement in
humans is supplied by intestinal bacteria.
Biotin and Avidin
• Addition of raw egg whites to the diet as a source of protein induces
symptoms of biotin deficiency, namely, dermatitis, glossitis, loss of
appetite, and nausea.
• Raw egg white contains a glyco-protein, avidin, which tightly binds
biotin and prevents its absorption from the intestine.
• With a normal diet, however, it has been estimated that 20 eggs/day
would be required to induce a deficiency syndrome.
• Eating raw eggs is generally not recommended due to the possibility
of salmonella infection.
Vitamin B3

Vitamin B7

Vitamin B5
Scenario 1
• A 60-year-old individual from a low-income community, whose diet
largely consists of polished white rice and instant noodles, gradually
develops inexplicable weakness in their legs, leading to a shuffling
gait. They also report persistent "pins and needles" sensations,
muscle tenderness, and eventually, a noticeable loss of muscle mass
in their lower limbs, making it difficult to stand unassisted. What
specific vitamin deficiency is the most probable cause?
Scenario 1
• A 60-year-old individual from a low-income community, whose diet
largely consists of polished white rice and instant noodles, gradually
develops inexplicable weakness in their legs, leading to a shuffling
gait. They also report persistent "pins and needles" sensations,
muscle tenderness, and eventually, a noticeable loss of muscle mass
in their lower limbs, making it difficult to stand unassisted. What
specific vitamin deficiency is the most probable cause?
Scenario 2
• A 45-year-old male, with a history of chronic alcohol consumption and
a poor diet, presents to the emergency room with severe shortness of
breath, rapid heart rate, and significant swelling in his lower legs and
feet. On examination, he has an enlarged heart and signs of fluid
overload in his lungs. Given his medical history and the sudden onset
of these cardiovascular symptoms, what specific vitamin deficiency
is highly suspected?
Scenario 2
• A 45-year-old male, with a history of chronic alcohol consumption and
a poor diet, presents to the emergency room with severe shortness of
breath, rapid heart rate, and significant swelling in his lower legs and
feet. On examination, he has an enlarged heart and signs of fluid
overload in his lungs. Given his medical history and the sudden onset
of these cardiovascular symptoms, what specific vitamin deficiency
is highly suspected?
Scenario 3
• A long-term alcoholic is brought in confused, disoriented, and
experiencing involuntary eye movements and an unsteady gait. When
questioned, he confidently describes elaborate, false memories of
recent events, despite clear evidence to the contrary. What is the
most likely diagnosis, and what crucial vitamin deficiency is
involved?
Scenario 3
• A long-term alcoholic is brought in confused, disoriented, and
experiencing involuntary eye movements and an unsteady gait. When
questioned, he confidently describes elaborate, false memories of
recent events, despite clear evidence to the contrary. What is the
most likely diagnosis, and what crucial vitamin deficiency is
involved?
Scenario 4
• A patient from a rural community, whose diet primarily consists of
corn, presents with a distinctive symmetrical rash on sun-exposed
skin that resembles a sunburn but is scaly and pigmented.
Concurrently, they report chronic diarrhea and recent onset of
memory loss, confusion, and even aggressive behavior. What
nutritional deficiency is indicated and why is their diet a risk factor?
Scenario 4
• A patient from a rural community, whose diet primarily consists of
corn, presents with a distinctive symmetrical rash on sun-exposed
skin that resembles a sunburn but is scaly and pigmented.
Concurrently, they report chronic diarrhea and recent onset of
memory loss, confusion, and even aggressive behavior. What
nutritional deficiency is indicated and why is their diet a risk factor?
Scenario 5
• An elderly patient, living alone with limited access to fresh produce,
presents with severe fatigue, swollen and bleeding gums, easy
bruising with pinpoint hemorrhages on the skin, and a chronic non-
healing wound on their leg. Upon further inquiry, their diet is found to
be deficient in fruits and vegetables. Based on this clinical picture,
what is the most likely diagnosis, and which specific vitamin
deficiency is responsible for these symptoms?
Scenario 5
• An elderly patient, living alone with limited access to fresh produce,
presents with severe fatigue, swollen and bleeding gums, easy
bruising with pinpoint hemorrhages on the skin, and a chronic non-
healing wound on their leg. Upon further inquiry, their diet is found to
be deficient in fruits and vegetables. Based on this clinical picture,
what is the most likely diagnosis, and which specific vitamin
deficiency is responsible for these symptoms?
Scenario 6
• A patient receiving long-term treatment with isoniazid for latent
tuberculosis infection begins to complain of tingling and numbness in
their hands and feet, which gradually progresses to a burning pain
and difficulty with fine motor movements. They also report some mild
unsteadiness when walking. What specific vitamin deficiency is the
likely cause of these neurological symptoms?
Scenario 6
• A patient receiving long-term treatment with isoniazid for latent
tuberculosis infection begins to complain of tingling and numbness in
their hands and feet, which gradually progresses to a burning pain
and difficulty with fine motor movements. They also report some mild
unsteadiness when walking. What specific vitamin deficiency is the
likely cause of these neurological symptoms?
Fat Soluble Vitamins
Vitamin K
• The principal role of vitamin K is in the post-translational
modification of various blood clotting factors.
• Serves as a coenzyme in the carboxylation of certain glutamic acid
residues present in these proteins.
• Exists in several forms:
• Plants → phylloquinone (or vitamin K1)
• Intestinal bacterial flora → menaquinone (or vitamin K2)
• Synthetic form → menadione
Functions:
• Vitamin K is required in the hepatic synthesis of prothrombin and
blood clotting factors II, VII, IX, and X. (2,7,9 and 10)
• These proteins are synthesized as inactive precursor molecules.
• Formation of the clotting factors requires the vitamin K–dependent
carboxylation of glutamic acid residues to Gla residues
• Reaction requires O2, CO2, and the hydroquinone form of vitamin K.
• Sensitive to inhibition by dicumarol, a naturally occuring
anticoagulant and by warfarin, a synthetic analog of vitamin K.
Interaction of prothrombin with
platelets:
• Gla residues of prothrombin are good chelators of positively charged
calcium ions, because of the two adjacent, negatively charged
carboxylate groups.
• The prothrombin–calcium complex is then able to bind to
phospholipids essential for blood clotting on the surface of platelets.
• Attachment to the platelet increases the rate at which the proteolytic
conversion of prothrombin to thrombin can occur.
Role of Gla residues in other
proteins:
• Gla is also present in other proteins
• Osteocalcin of bone
• Protein C involved in limiting the formation of blood clots.
Distribution and requirement of
vitamin K
• Vitamin K is found in:
• Cabbage
• Kale
• Spinach
• Egg yolk
• Liver
• Extensive synthesis of the vitamin by the bacteria in the gut.
• AI for vitamin K is 120 μg/day for adult males and 90 μg for adult
females.
Clinical Indications:
• True vitamin K deficiency is unusual because adequate amounts are
generally produced by intestinal bacteria or obtained from the diet.
• If bacterial population in the gut is decreased, for example, by
antibiotics, the amount of formed vitamin is depressed, and this can
lead to hypoprothrombinemia in malnourished individual.
• Condition may require supplementation with vitamin K to correct the
bleeding tendency.
• Certain second-generation cephalosporins, for example,
cefoperazone, cefamandole, and moxalactam cause
hypoprothrombinemia, apparently by a warfarin-like mechanism.
• Their use in treatment is usually supplemented with vitamin K.
Deficiency of vitamin K in the
newborn
• Newborns have sterile intestines and so initially lack the bacteria that
synthesize vitamin K.
• Human milk provides only about one-fifth of the daily requirement for
vitamin K.
• It is recommended that all newborns receive a single intramuscular
dose of vitamin K as prophylaxis against hemorrhagic disease.
Toxicity of vitamin K
• Prolonged administration of large doses of synthetic vitamin K
(menadione) can produce:
• Hemolytic anemia
• Jaundice
• Due to toxic effects on the membrane of red blood cells; therefore, it is no
longer used to treat vitamin K deficiency.
• No UL has been set for vitamin K.
Vitamin E
• The E vitamins consist of eight naturally
occurring tocopherols
• α-tocopherol is the most active.
• The primary function of vitamin E is as an
antioxidant in prevention of the nonenzymic
oxidation of cell components, for example,
polyunsaturated fatty acids (PUFAs) by
molecular oxygen and free radicals.
Distribution and requirements of
vitamin E
• Vegetable oils are rich sources of vitamin E
• Liver and eggs contain moderate amounts.
• The RDA for α-tocopherol is 15 mg for adults.
• Vitamin E requirement increases as the intake of polyunsaturated
fatty acid increases.
Distribution and requirements of
vitamin E
• Deficiency is almost entirely restricted to premature infants.
• In adults, it is usually associated with defective lipid absorption or
transport.
• Signs of human vitamin E deficiency include sensitivity of erythrocytes
to peroxide, and the appearance of abnormal cellular membranes.
Distribution and requirements of
vitamin E
• Vitamin E is not recommended for the prevention of chronic disease,
such as coronary heart disease or cancer.
• Clinical trials using vitamin E supplementation have been uniformly
disappointing.
• For example, subjects in the Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Study trial who received high doses of vitamin E not only
lacked cardiovascular benefit but also had an increased incidence of
stroke.
Toxicity of vitamin E
• Vitamin E is the least toxic of the fat-soluble vitamins, and no toxicity
has been observed at doses of 300 mg/day
Thankyou!